Guanylate cyclase activity was reduced in soluble fractions from rat liver slices incubated with diamide, N-ethylmaleimide, or 5',5'-dithiobis-2-nitrobenzoate; addition of GSH or dithiothreitol to assays restored activity. Inactivation of purified rat liver guanylate cyclase by p-hydroxymercuribenzoate at 0 degrees C. It appears that guanylate cyclase activity in intact cells could be modulated by reversible modification of critical sulfhydryl groups, e.g., by thiol:disulfide exchange involving glutathione. Fusion of spleen cells from immunized mice with myeloma cells has yielded some hybrids that appear to be producing antibodies to the guanylate cyclase and these are being cloned.